The neuroligins and their neurexin ligands: from structure to function at the synapse - Aix-Marseille Université Access content directly
Journal Articles Journal of Molecular Neuroscience Year : 2014

The neuroligins and their neurexin ligands: from structure to function at the synapse

Abstract

The neuroligins are cell adhesion proteins whose extracellular domain belongs to the α/β-hydrolase fold family of proteins, mainly containing enzymes and exemplified by acetylcholinesterase. The ectodomain of postsynaptic neuroligins interacts through a calcium ion with the ectodomain of presynaptic neurexins to form flexible trans-synaptic associations characterized by selectivity for neuroligin or neurexin subtypes. This heterophilic interaction, essential for synaptic differentiation, maturation, and maintenance, is regulated by gene selection, alternative mRNA splicing, and posttranslational modifications. Mutations leading to deficiencies in the expression, folding, maturation, and binding properties of either partner are associated with autism spectrum disorders. The currently available structural and functional data illustrate how these two families of cell adhesion molecules bridge the synaptic cleft to participate in synapse plasticity and support its dynamic nature. Neuroligin partners distinct from the neurexins, and which may undergo either trans or cis interaction, have also been described, and tridimensional structures of some of them are available. Our study emphasizes the partnership versatility of the neuroligin ectodomain associated with molecular flexibility and alternative binding sites, proposes homology models of the structurally non-characterized neuroligin partners, and exemplifies the large structural variability at the surface of the α/β-hydrolase fold subunit. This study also provides new insights into possible surface binding sites associated with non-catalytic properties of the acetylcholinesterase subunit.
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Dates and versions

hal-03270068 , version 1 (18-04-2023)

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Yves Bourne, Pascale Marchot. The neuroligins and their neurexin ligands: from structure to function at the synapse. Journal of Molecular Neuroscience, 2014, 53, pp.387-396. ⟨10.1007/s12031-014-0234-6⟩. ⟨hal-03270068⟩
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